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ASCO 2026 | Alterations in calreticulin and CD47 expression dynamics in myeloid malignancies
Ciro Rinaldi, MD, PhD, United Lincolnshire Teaching Hospital and University of Lincoln, Lincoln, UK, shares insights into his work investigating alterations in calreticulin and CD47 expression dynamics in myeloid malignancies, including myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs), highlighting that CD47 overexpression is associated with resistance to certain treatments. Prof. Rinaldi notes that his team is also investigating the role of macrophage polarization in CD47 and calreticulin deregulation and exploring the potential of macrophage checkpoint inhibitors as a new therapeutic approach. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
We recently published in Hematologica a study where we looked at the expression of CD47 and calreticulin in myeloid cancer patients, particularly myelodysplastic syndromes and myeloproliferative disorders. We previously demonstrated that CD47 was overexpressed in some of those patients, and we demonstrated that the expression of calreticulin could be differentiated depending on treatment and depending on treatment response, etc...
We recently published in Hematologica a study where we looked at the expression of CD47 and calreticulin in myeloid cancer patients, particularly myelodysplastic syndromes and myeloproliferative disorders. We previously demonstrated that CD47 was overexpressed in some of those patients, and we demonstrated that the expression of calreticulin could be differentiated depending on treatment and depending on treatment response, etc. What we looked at was the potential implication of the level of expression up front or during treatment and the response to treatment and the potential outcome. What we found is that CD47 is not only wrongly regulated at the start, so it’s upregulated at disease diagnosis, but in patients that are not responding to treatment, for example, in MDS, patients that are not responding to azacitidine, the level of expression of the CD47 is higher. So the anti-phagocytic signal that CD47 is giving translates into a resistance to some drugs.
What we are now trying to also understand is whether some of the previous drug development, such as anti-CD47, anti-CIRP-alpha agent, failed in phase three trials, probably because it’s not just about CD47 deregulation, but it’s also about who is going to respond to deregulation of CD47, and I’m thinking about macrophages. So a line of research that we’re now conducting in my lab is understanding the damage that macrophages might have also, you know, they might also experience as part of the myeloid disorder, whether the polarization of the macrophages has any implication in not responding to the CD47 or the calreticulin message, and whether there is anything that we can do to repolarize in the right way. And it will take some time to understand. But there are some new drugs that are potentially of benefit by repolarizing macrophages and what we would call now macrophage checkpoint inhibitors, which we never had in the pipeline. And there’s some interesting data in AML, which we want to also look into in MPN.
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